Early Therapeutic Prediction Based on Tumor Hemodynamic Response Imaging: Clinical Studies in Breast Cancer with Time-Resolved Diffuse Optical Spectroscopy

Abstract

This study reports data from three clinical studies using the time-resolved diffuse optical spectroscopy (TRS) system among breast cancer patients. The parameters of oxy-hemoglobin (O2Hb), deoxy-hemoglobin (HHb), total hemoglobin (tHb), and oxygen saturation (SO2) were evaluated using TRS, and its efficacy was tested in three trials. In trial 1, we recruited 118 patients with primary breast cancer to estimate the tumor detection rate. The cumulative detection rate was 62.7%, while that in T stage 0 was 31.3% and in T stage 1 was 44.7%. These were lower than those of T stage 2 (78.9%) and T stage 3 (100%). Next, we used TRS to monitor tumor hemodynamic response to neoadjuvant chemotherapy (n = 100) and found that pathological complete response (pCR) tumors had significantly lower tumor tHb than non-pCR tumors; a similar result was observed in estrogen receptor (ER)-negative tumors, but not in ER-positive tumors. The third trial monitored hemodynamic response to antiangiogenic therapy, bevacizumab (n = 28), and we demonstrated that sequential optical measurement of tumor SO2 might be useful for detecting acute hypoxia 1–3 days after bevacizumab initiation. Next, response monitoring of neoadjuvant endocrine therapy (n = 30) suggested that changes in tumor tHb during treatment can predict and distinguish between responsive and non-responsive tumors early in letrozole therapy. In conclusion, our results show that hemodynamic monitoring of tumors by TRS could pair the unique features of tumor physiology to drug therapy and contribute to patient-tailored medicine. We recently established a platform for performing TRS in patients with breast cancer.

Special Issue on New Horizons in Time Domain Diffuse Optical Spectroscopy and Imaging

“…Five of 10 original papers deal with clinical applications that utilize the strengths of TD measurements. Ueda and Saeki applied TD DOS to three studies on breast cancer, reporting the detection rate of breast cancer, tumor hemodynamic responses to neoadjuvant chemotherapy, and antiangiogenic therapy [16]. Kinoshita et al, who measured skeletal muscle oxygenation in the lower extremities during 3 h of continuous sitting, report that compression stockings suppress increases in extracellular water in the lower extremities, leading to reduced blood volume and oxygenation levels in skeletal muscles [17].…”

Changes in the tumor oxygenation but not in the tumor volume and tumor vascularization reflect early response of breast cancer to neoadjuvant chemotherapy

“…Optical methods based on the difference in the scattering and absorption properties of normal and tumor tissues have been actively developed for diagnosis [19,20] and monitoring of breast pathology [21,22,23,24]. Diffuse optical spectroscopy imaging (DOSI) utilizes light of far-red and near-infrared spectral range (~ 650-1000 nm), which has low attenuation rate in tissue.…”